For the past 21 years, the J. Craig Venter Institute (JCVI) has applied leading edge genomics approaches to diverse problems in biology. Through significant changes in sequencing technology, an emphasis has been maintained on establishing a robust sample and data handling infrastructure and computational analysis tools to take advantage of increasingly large and complex genomic and transcriptomic datasets. The JCVI Genomic Center for Infectious Diseases (GCID) is built around a central theme - the application of innovative genomics-based approaches to study pathogens and determinants of their virulence, drug resistance, immune-evasion, and interactions with the host and the host microbiome. The JCVI GCID will address critical issues in pathogen biology including (among others), the evolutionary dynamics of viruses in human hosts and animal reservoirs, the dissemination of antibiotic resistance in bacteria, the search for novel antifungal drug targets, and the basis for immunity to malaria infection by Plasmodium falciparum. The hypothesis-driven Research Projects will be supported by a Technology Core and a Data Management and Analysis and Resource Dissemination (DMARD) Core. An Administrative Core will assure effective management and integration of the Program components so as to take best advantage of shared approaches, samples, and insights. An outreach program will be established to promote the use of genomics in other institutions and countries. All of the data, software tools, and strain resources will rapidly be made publicly available to support the broadest use by the scientific community. The impact of the JCVI Program will prove to be very high as it addresses the basic science issues that will underpin solutions to some of the major problems and challenges in the prevention and management of infectious diseases today. RELEVANCE: The threat to public health by infectious diseases is increasing due to rapid emergence of drug resistance, and evolving pathogens, an aging population, and the threat of the use of infectious disease agents as bioweapons. The JCVI Genomic Center for infectious diseases will apply innovative genomic technologies to develop Infectious Diseases biology to meet the major problems and challenges in the prevention and management of infectious diseases. Project 1: Exploiting Viral Genomics to Understand Disease Project Leader (PL): David Wentworth DESCRIPTION (as provided by applicant): Research Project 1 focuses on significant endemic viral pathogens from humans and viruses from animal hosts that have strong zoonotic potential. High-throughput whole-genome next-generation sequencing (NGS), combined with bioinformatics algorithms, will be used to sequence and analyze the genomes from more than 10,000 strains representing seven viral species. This will characterize the genetic diversity over a range of virus families, including many NIAID priority pathogens, to understand critical evolutionary mechanisms central to viral evolution, pathogenesis, transmission, and/or antiviral resistance. Specifically we aim to: 1) compare and contrast the genetic diversity and evolutionary dynamics of viruses circulating within and/or between humans and animal reservoirs, 2) elucidate viral-host-microbiome determinants that influence viral pathogenesis, and 3) perform deep sequencing to understand intra-host viral diversity, transmission dynamics, and antiviral resistance. Collectively, this project will use multiple genomics approaches (e.g., genomic sequencing, metagenomics, and transcriptomics) to provide the scientific community with genomic data sets of broad use from important viral families. These data will be analyzed using phylogenetics and other bioinformatics algorithms to show the spatial and temporal evolution of these pathogens. Finally, the data generated will identify, track, and predict antigenic drift/shift, recombination, escape from natural or vaccine-induced host immune responses, antiviral resistance, inter- and intra-species transmission, and the response of a host's commensal microbiota to viral infection. The information generated from these studies will help us to produce superior vaccines and antivirals, and the data sets will prove critical for rapid responses to the emergence of novel pathogens (i.e., pandemic preparedness) that arise naturally or as a result of bioterrorism. RELEVANCE: Viruses are global pathogens that cause significant disease in humans. Frequent transmission of animal viruses to human hosts and human-to-human transmission result in outbreaks, epidemics, or pandemics. Therefore, Project 1 will target significant and emerging viral pathogens from human and animal hosts for genome sequencing in an effort to sequence virus species that could significantly impact public health.